Diagnosis of primary hepatocellular carcinoma (HCC) at early stages has obviously been improved since determination of serum levels of free alpha-fetoprotein (AFP) was implemented. AFP has been considered as the standard tumor marker of primary HCC, although certain patients have very low serum free AFP levels. In the present study, clinical application of measuring serum AFP-IgM immune complexes compared to the serum free AFP was evaluated for diagnosis of small HCC. One hundred and three healthy controls, 74 patients with primary HCC, 27 patients with liver cirrhosis and 63 patients with chronic hepatitis were included in the present study. Serum levels of AFP-IgM immune complexes and free AFP were determined by ELISA and electrochemiluminescence, respectively. The best cut-off values of AFP-IgM immune complexes and free AFP for the diagnosis of primary HCC were 300 AU/ml and 10 μg/l, respectively, according to the area under the curve (AUC). At these cut-off values, the sensitivities of AFP-IgM and AFP for HCC were 64.9% and 79.7%, respectively, with specificities of 75.6% and 80.3%, respectively. Combining positivity for both tumor markers, the specificity and accuracy of diagnosis of HCC were 89.1% and 79.0%, respectively. Moreover, when the diameter of the tumor was ≤ 3 cm (being considered as small HCC), the sensitivity and specificity were 100.0% and 75.3%, respectively. There was no significant correlation between AFP-IgM level, patient sex or age (p>0.05). The ROC area was significantly different between AFP-IgM and AFP (Z = 2.19, p = 0.0286). In addition, the serum AFP-IgM levels were significantly higher in the patients with tumor diameter ≤ 3 cm (1090.4 ± 571.8 AU/ml) than in the patients with tumor diameter >3 cm (604.9 ± 749.9 AU/ml). It is concluded that determining serum levels of both AFP-IgM immune complex and AFP may have potential benefit for the diagnosis of small HCC.